CN113912530A - Treatment method of 4-AA intermediate waste liquid - Google Patents
Treatment method of 4-AA intermediate waste liquid Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 45
- 239000007788 liquid Substances 0.000 title claims abstract description 39
- 239000002699 waste material Substances 0.000 title claims abstract description 23
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims abstract description 52
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims abstract description 26
- HQWKKEIVHQXCPI-UHFFFAOYSA-L disodium;phthalate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C([O-])=O HQWKKEIVHQXCPI-UHFFFAOYSA-L 0.000 claims abstract description 18
- 238000010511 deprotection reaction Methods 0.000 claims abstract description 14
- 238000010438 heat treatment Methods 0.000 claims abstract description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 13
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 13
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 13
- 239000006227 byproduct Substances 0.000 claims abstract description 13
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 11
- 238000010992 reflux Methods 0.000 claims abstract description 11
- POVYRDDXMXYEJS-UHFFFAOYSA-N 2-[bis(2-hydroxyethyl)carbamoyl]benzoic acid Chemical compound OCCN(CCO)C(=O)C1=CC=CC=C1C(O)=O POVYRDDXMXYEJS-UHFFFAOYSA-N 0.000 claims abstract description 10
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 238000001816 cooling Methods 0.000 claims abstract description 9
- 238000001914 filtration Methods 0.000 claims abstract description 9
- 238000005406 washing Methods 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000004821 distillation Methods 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 239000000463 material Substances 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 230000002255 enzymatic effect Effects 0.000 claims description 11
- -1 N, N-di (2-hydroxyethyl) phthalic acid diamide Chemical compound 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims 1
- 239000002920 hazardous waste Substances 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 8
- 230000007613 environmental effect Effects 0.000 abstract description 6
- 102000004190 Enzymes Human genes 0.000 abstract description 5
- 108090000790 Enzymes Proteins 0.000 abstract description 5
- 239000003814 drug Substances 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 3
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229940041011 carbapenems Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OEYMQQDJCUHKQS-UHFFFAOYSA-N (4-oxoazetidin-2-yl) acetate Chemical compound CC(=O)OC1CC(=O)N1 OEYMQQDJCUHKQS-UHFFFAOYSA-N 0.000 description 1
- BRONALLIAIBEPV-UHFFFAOYSA-N 4-(2-hydroxyethyl)isoindole-1,3-dione Chemical compound OCCC1=CC=CC2=C1C(=O)NC2=O BRONALLIAIBEPV-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- JUZNIMUFDBIJCM-ANEDZVCMSA-N Invanz Chemical compound O=C([C@H]1NC[C@H](C1)SC=1[C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)NC1=CC=CC(C(O)=O)=C1 JUZNIMUFDBIJCM-ANEDZVCMSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- TYMABNNERDVXID-DLYFRVTGSA-N Panipenem Chemical compound C([C@@H]1[C@H](C(N1C=1C(O)=O)=O)[C@H](O)C)C=1S[C@H]1CCN(C(C)=N)C1 TYMABNNERDVXID-DLYFRVTGSA-N 0.000 description 1
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229960002770 ertapenem Drugs 0.000 description 1
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 1
- 229960002182 imipenem Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229960002260 meropenem Drugs 0.000 description 1
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229950011346 panipenem Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of chemical synthesis, and discloses a method for treating 4-AA intermediate waste liquid, which comprises the following three steps: (1) heating N, N-di (2-hydroxyethyl) phthalic acid amide and an alkaline catalyst in an aqueous solution for reflux reaction to prepare sodium phthalate feed liquid; (2) carrying out reduced pressure distillation on the sodium phthalate material liquid obtained in the step (1) to obtain ethanolamine, and adjusting the acid of the residual residues to prepare phthalic acid; (3) and (2) introducing ammonia gas or adding ammonia water into a reaction kettle containing phthalic acid for heating reaction, cooling after the reaction is finished, adding water for washing, crystallizing, filtering and drying to obtain the phthalimide. The method converts the byproduct hazardous waste generated in the deprotection step of the enzyme method 4-AA into the starting raw material of the enzyme method 4-AA, changes the hazardous waste into valuable, effectively reduces the raw material cost, effectively reduces the storage, transportation and treatment cost of the hazardous waste, and has obvious economic benefit and environmental benefit.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a method for treating 4-AA intermediate waste liquid.
Background
4-AA is 4-acetoxyazetidinone for short, is a main raw material for producing carbapenem (namely penem) antibiotics raw material medicaments, and is used for synthesizing mother nucleus of penem antibiotics such as meropenem, panipenem, ertapenem, imipenem and the like; carbapenem is a novel antibiotic with a brand new chemical structure developed in the last 70 th century of the United states, is formed by structural modification of penicillin, and belongs to 'beta lactam antibiotics' with penicillin and cephalosporin; the wide application of antibiotics at present leads the drug resistance of bacteria to be continuously increased, and brings new challenges to clinical anti-infection treatment; the carbapenem antibiotics have high activity and wide antibacterial spectrum to various drug-resistant bacteria and become powerful weapons for clinically resisting the drug-resistant strains; with the intensive research on the structure, antibacterial activity and clinical effect of carbapenems and the continuous emergence of new carbapenems, it is expected to become a first-line drug for treating severe infection.
At present, a first synthetic route taking L-threonine as an initial raw material is commonly adopted in the 4-AA synthetic process, and the process is called a 4-AA chemical method synthetic route for short, and has the characteristics that the raw materials are cheap, the cost is relatively low, but more three wastes are generated, ozone is used for oxidation in an ozone special reactor, the danger coefficient is high, the current situation of safety and environmental protection policies is not met, and the elimination is faced step by step; the process is characterized by relatively less three wastes and mild reaction conditions, and accords with the current national security and environmental protection policy; however, when an intermediate in this step (which we refer to as a deprotection step) is synthesized by using ethanolamine, methanol and N-heptane, a dangerous by-product N, N-bis (2-hydroxyethyl) phthalimide is produced; for each ton of 4-AA produced, taking the phthalimide process as an example, about 1.1 ton of hazardous waste is generated in the deprotection step. Under the severe environment of current safety and environmental protection, the generation of process hazardous wastes is reduced, and the process is greatly advanced towards more environmental protection.
The invention patent with application number 201910284445.X and publication number CN109879904A discloses a method for preparing a penem drug intermediate 4-AA precursor and an intermediate 4-AA, and describes how to prepare 4-AA, but does not relate to the 4-AA enzymatic synthesis, and does not relate to the treatment of intermediate waste liquid.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a method for treating 4-AA intermediate waste liquid, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and the method comprises the following steps:
(1) heating N, N-di (2-hydroxyethyl) phthalic acid amide and an alkaline catalyst in an aqueous solution for reflux reaction to prepare sodium phthalate feed liquid;
(2) carrying out reduced pressure distillation on the sodium phthalate material liquid obtained in the step (1) to obtain ethanolamine, and adjusting the acid of the residual residues to prepare phthalic acid;
(3) and (2) introducing ammonia gas or adding ammonia water into a reaction kettle containing phthalic acid for heating reaction, cooling after the reaction is finished, adding water for washing, crystallizing, filtering and drying to obtain the phthalimide.
The above technical solution can be further optimized as follows:
the alkaline catalyst in the step (1) is one or a mixture of sodium hydroxide, potassium hydroxide and lithium hydroxide.
The molar ratio of the N, N-bis (2-hydroxyethyl) phthalic acid amide to the basic catalyst in the step (1) is 1 (0.5-2.5).
And (2) heating in the step (1) to carry out reflux reaction at the temperature of 80-240 ℃ for 15-30 h.
And (3) the ethanolamine distilled out in the step (2) is continuously used for a deprotection step in the 4-AA enzymatic synthesis route.
And (3) adjusting the pH to 6.5-7 during the acid adjustment in the step (2).
And (3) one or more of hydrochloric acid, sulfuric acid and acetic acid is/are mixed during acid adjustment in the step (2).
The molar ratio of the phthalic acid to the ammonia water or ammonia gas in the step (3) is 1 (1.5-3.5).
The step (3) is heated for reaction, the reaction temperature is 150 ℃ and 250 ℃, and the reaction time is 15-25 h.
The drying temperature in the step (3) is 80-100 ℃.
Compared with the prior art, the invention mainly has the following beneficial technical effects:
1. the method converts the byproduct hazardous waste generated in the deprotection step of the enzyme method 4-AA into the starting raw material of the enzyme method 4-AA, changes the hazardous waste into valuable, effectively reduces the raw material cost, effectively reduces the storage, transportation and treatment cost of the hazardous waste, and has obvious economic benefit and environmental benefit.
2. The by-product ethanolamine can be continuously used in the process of the enzyme method 4-AA, and the cyclic utilization is successfully realized.
3. The ammonia water or ammonia gas used in the invention is from a byproduct in another workshop, and the ammonia water or ammonia gas is successfully recycled and reused.
4. The method is reasonable, simple and convenient to operate and beneficial to popularization.
The reaction structure of the invention is as follows:
Detailed Description
The present invention will be described in detail with reference to examples.
Example 1
A method for treating 4-AA intermediate waste liquid, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic acid diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and the method comprises the following steps:
(1) putting N, N-di (2-hydroxyethyl) phthalic acid amide and potassium hydroxide into a reaction kettle according to the molar ratio of 1:2, heating the mixture in an aqueous solution to 120 ℃, and carrying out reflux reaction for 25 hours to prepare sodium phthalate feed liquid.
(2) And (2) carrying out reduced pressure distillation on the sodium phthalate feed liquid obtained in the step (1) to obtain ethanolamine, and adjusting the pH of the residual residue to 6.5-7 by using 25% hydrochloric acid to prepare phthalic acid.
(3) Adding 17% ammonia water into a reaction kettle containing phthalic acid, wherein the molar ratio of the phthalic acid to the ammonia water is 1:3.5, reacting for 18 hours at the temperature of 240 ℃, cooling, adding water for washing after the reaction is finished, crystallizing, filtering and drying at the temperature of 100 ℃ to obtain phthalimide; the yield was 91%.
Example 2
A method for treating 4-AA intermediate waste liquid, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic acid diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and the method comprises the following steps:
(1) putting N, N-di (2-hydroxyethyl) phthalic acid amide and sodium hydroxide into a reaction kettle according to the molar ratio of 1:2, heating the mixture in an aqueous solution to 120 ℃, and carrying out reflux reaction for 30 hours to prepare sodium phthalate feed liquid.
(2) And (2) carrying out reduced pressure distillation on the sodium phthalate feed liquid obtained in the step (1) to obtain ethanolamine, and adjusting the pH of the residual residue to 6.5-7 by using 25% hydrochloric acid to prepare phthalic acid.
(3) Adding 17% ammonia water into a reaction kettle containing phthalic acid, wherein the molar ratio of the phthalic acid to the ammonia water is 1:3.5, reacting for 20 hours at the temperature of 240 ℃, cooling, adding water for washing after the reaction is finished, crystallizing, filtering and drying at the temperature of 100 ℃ to obtain phthalimide; the yield was 90%.
Example 3
A method for treating 4-AA intermediate waste liquid, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic acid diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and the method comprises the following steps:
(1) putting N, N-di (2-hydroxyethyl) phthalic acid amide and lithium hydroxide into a reaction kettle according to the molar ratio of 1:2, heating the reaction kettle in an aqueous solution to 120 ℃, and carrying out reflux reaction for 30 hours to prepare sodium phthalate feed liquid.
(2) And (2) carrying out reduced pressure distillation on the sodium phthalate feed liquid obtained in the step (1) to obtain ethanolamine, and adjusting the pH of the residual residue to 6.5-7 by using 25% hydrochloric acid to prepare phthalic acid.
(3) Adding 17% ammonia water into a reaction kettle containing phthalic acid, wherein the molar ratio of the phthalic acid to the ammonia water is 1:3.5, reacting for 25 hours at the temperature of 240 ℃, cooling, adding water for washing after the reaction is finished, crystallizing, filtering and drying at the temperature of 100 ℃ to obtain phthalimide; the yield was 87%.
Example 4
A method for treating 4-AA intermediate waste liquid, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic acid diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and the method comprises the following steps:
(1) adding N, N-bis (2-hydroxyethyl) phthalic acid amide and sodium hydroxide into a reaction kettle according to the molar ratio of 1:0.5, heating to 80 ℃ in an aqueous solution, and carrying out reflux reaction for 15 hours to prepare sodium phthalate feed liquid.
(2) And (2) carrying out reduced pressure distillation on the sodium phthalate feed liquid obtained in the step (1) to obtain ethanolamine, and adjusting the pH of the residual residue to 6.5-7 by using 10% sulfuric acid to prepare phthalic acid.
(3) Adding ammonia gas into a reaction kettle containing phthalic acid, wherein the molar ratio of the phthalic acid to the ammonia gas is 1:1.5, reacting for 25 hours at the temperature of 150 ℃, cooling, adding water for washing after the reaction is finished, crystallizing, filtering and drying at the temperature of 80 ℃ to obtain phthalimide; the yield was 60%.
Example 5
A method for treating 4-AA intermediate waste liquid, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic acid diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and the method comprises the following steps:
(1) putting N, N-di (2-hydroxyethyl) phthalic acid amide and sodium hydroxide into a reaction kettle according to the molar ratio of 1:2.5, heating the mixture in an aqueous solution to 240 ℃, and carrying out reflux reaction for 20 hours to prepare sodium phthalate feed liquid.
(2) And (2) carrying out reduced pressure distillation on the sodium phthalate feed liquid obtained in the step (1) to obtain ethanolamine, and adjusting the pH of the residual residues to 6.5-7 by using acetic acid to prepare phthalic acid.
(3) Adding ammonia gas into a reaction kettle containing phthalic acid, wherein the molar ratio of the phthalic acid to the ammonia gas is 1:3.5, reacting for 15 hours at the temperature of 250 ℃, cooling, adding water for washing after the reaction is finished, crystallizing, filtering and drying at the temperature of 100 ℃ to obtain phthalimide; the yield was 73%.
Example 6
A method for treating 4-AA intermediate waste liquid, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic acid diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and the method comprises the following steps:
(1) adding N, N-di (2-hydroxyethyl) phthalic diamide and mixed alkali prepared from potassium hydroxide, sodium hydroxide and lithium hydroxide in a mass ratio of 1:1:1 into a reaction kettle according to a molar ratio of 1:2.5, heating to 240 ℃ in an aqueous solution, and carrying out reflux reaction for 20 hours to prepare sodium phthalate feed liquid.
(2) And (2) distilling the sodium phthalate feed liquid obtained in the step (1) under reduced pressure to obtain ethanolamine, and adjusting the pH of the residual residue to 6.5-7 by using mixed acid prepared from hydrochloric acid, sulfuric acid and acetic acid according to the mass ratio of 1:1:1 to prepare phthalic acid.
(3) Adding ammonia gas into a reaction kettle containing phthalic acid, wherein the molar ratio of the phthalic acid to the ammonia gas is 1:3.5, reacting for 15 hours at the temperature of 250 ℃, cooling, adding water for washing after the reaction is finished, crystallizing, filtering and drying at the temperature of 100 ℃ to obtain phthalimide; the yield was 71%.
Claims (10)
1. A treatment method of 4-AA intermediate waste liquid is provided, wherein the 4-AA intermediate is a by-product N, N-di (2-hydroxyethyl) phthalic acid diamide generated in a deprotection step in a 4-AA enzymatic synthesis route, and is characterized by comprising the following steps:
(1) heating N, N-di (2-hydroxyethyl) phthalic acid amide and an alkaline catalyst in an aqueous solution for reflux reaction to prepare sodium phthalate feed liquid;
(2) carrying out reduced pressure distillation on the sodium phthalate material liquid obtained in the step (1) to obtain ethanolamine, and adjusting the acid of the residual residues to prepare phthalic acid;
(3) and (2) introducing ammonia gas or adding ammonia water into a reaction kettle containing phthalic acid for heating reaction, cooling after the reaction is finished, adding water for washing, crystallizing, filtering and drying to obtain the phthalimide.
2. The method for treating the 4-AA intermediate waste liquid as claimed in claim 1, wherein the alkaline catalyst in the step (1) is one or a mixture of sodium hydroxide, potassium hydroxide and lithium hydroxide.
3. The method for treating the 4-AA intermediate waste liquid according to claim 1, wherein the molar ratio of the N, N-bis (2-hydroxyethyl) phthalic acid amide to the basic catalyst in the step (1) is 1 (0.5-2.5).
4. The method for treating 4-AA intermediate waste liquid according to claim 1, wherein the heating in the step (1) is carried out for reflux reaction at 80-240 ℃ for 15-30 h.
5. The method for treating 4-AA intermediate waste liquid according to claim 1, wherein the ethanolamine distilled in the step (2) is used for deprotection step in the 4-AA enzymatic synthesis route.
6. The method for treating 4-AA intermediate waste liquid according to claim 1, wherein the pH is adjusted to 6.5-7 during the acid adjustment in the step (2).
7. The method for treating the 4-AA intermediate waste liquid as claimed in claim 1, wherein one or more mixed acids selected from hydrochloric acid, sulfuric acid and acetic acid are adopted during the acid adjustment in the step (2).
8. The method for treating 4-AA intermediate waste liquid according to claim 1, wherein the molar ratio of phthalic acid to ammonia water or ammonia gas in the step (3) is 1 (1.5-3.5).
9. The method as claimed in claim 1, wherein the step (3) is carried out at a temperature of 150 ℃ and 250 ℃ for a period of 15-25 h.
10. The method for treating 4-AA intermediate waste liquid according to claim 1, wherein the drying temperature in the step (3) is 80-100 ℃.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001122858A (en) * | 1999-10-22 | 2001-05-08 | Kawasaki Kasei Chem Ltd | Production of phthalimide compound |
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